BM, which are a frequent complication in patients with NSCLC, is associated with poor survival outcomes and poses clinical challenges for oncologists[8]. At initial diagnosis, 10% of NSCLC patients have BM, and the brain is the only site of tumor relapse in 50% NSCLC patients[9]. However, in NSCLC patients harboring ALKr, the risk of BM is higher. The rate of BM is approximately 20% in NSCLC patients harboring ALKr at initial diagnosis and up to 75% in these patients by using crizotinib[10]. So, the therapeutic effect of BM plays an important role in prolonging overall survival and improving the quality of life. However, there isn’t a standard therapeutic mode in BM of NSCLC. A large number of studies have taken different strategies to treat BM of NSCLC, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, and combination of different modes[11–15].
As well as this patient, radiotherapy plays an important role in treating BM of NSCLC harbouring driver-gene mutation, such as WBRT[13, 16, 17], stereotactic radiosurgery (SRS)[16–18], and so on. According to National Comprehensive Cancer Network (NCCN) recommendation, the patient was given the WBRT. In order to increase the local control, we used SIB to increase the dose of metastatic focuses. However, during the course of radiotherapy, it was unexpected that the number of the brain metastasis inexplicably increased in our case. The phenomenon has not been reported. The current studies mainly focus on that WBRT impairs cognitive function and quality of life and SRS is an alternative therapy for BM. Some studies showed that SRS obtained good local control and less cognitive deterioration in treating 1 to 3 brain metastases[19, 20]. Hughes RT et al reported that SRS alone adapted to treat these patients with 5 to 15 BM[21]. Recently, Robin TP et al found that BM patients with ALKr may be uniquely suited to benefit from SRS[20]. So, SRS alone may become a preferred strategy in treating brain metastases.
ALKr wasn`t found in blood sample of the patient by NGS. The patients didn`t continued in using ALK inhibitor. If the patient was an ALK-positive in blood sample, the patient had combined radiotherapy with alectinib. Because of poor accumulation of crizotinib in CNS, many NSCLC patients with ALKr frequently experience BM after treatment with crizotinib. The second generation ALK inhibitor, that is alectinib, can retain a higher concentration in the CNS and enhance the efficacy in treating BM in NSCLC patients with ALKr[22]. After crizotinib failure for ALK-positive NSCLC patients, Novello S et al reported that alectinib significantly improved the efficacy of BM compared with chemotherapy[3]. Whether radiotherapy or TKIs or combined radiotherapy with TKIs can improved the efficacy of BM? By meta-analysis, Singh R et al reported that there was no significant difference between combined radiotherapy with TKIs compared with radiotherapy alone. Similarly, there was no significant difference in median overall survival among TKIs alone, radiotherapy alone, and a combination of TKIs and radiotherapy[13]. So, the choice of three modes should be determined according to the specific situation of the patient. In our case, the patient was empirically used alectinib after radiotherapy failure. It achieved unexpected success in our patient.
In summary, we got some enlightenment form the patient. Firstly, liquid biopsy is complementary to tissue biopsy in NSCLC, mainly in EGFR mutation. However, ALK detection should use tissue biopsy as much as possible. Secondly, we suggest the BM patient of NSCLC use the second generation TKI, such as alectinib, ceritinib, after resistance to crizotinib whether ALKr is positive or negative in liquid biopsy. Lastly, we believe that combined radiotherapy with TKIs is an optimal mode in the BM patient of NSCLC after resistance to crizotinib.